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Design and Estimation for Evaluating Principal Surrogate Markers in Vaccine Trials

Design and estimation for evaluating principal surrogate markers in vaccine trials
Authors: Huang, Ying; Gilbert, Peter B.; Wolfson, Julian;

Design and Estimation for Evaluating Principal Surrogate Markers in Vaccine Trials

Abstract

AbstractSummaryIn vaccine research, immune biomarkers that can reliably predict a vaccine's effect on the clinical endpoint (i.e., surrogate markers) are important tools for guiding vaccine development. This article addresses issues on optimizing two‐phase sampling study design for evaluating surrogate markers in a principal surrogate framework, motivated by the design of a future HIV vaccine trial. To address the problem of missing potential outcomes in a standard trial design, novel trial designs have been proposed that utilize baseline predictors of the immune response biomarker(s) and/or augment the trial by vaccinating uninfected placebo recipients at the end of the trial and measuring their immune biomarkers. However, inefficient use of the augmented information can lead to counter‐intuitive results on the precision of estimation. To remedy this problem, we propose a pseudo‐score type estimator suitable for the augmented design and characterize its asymptotic properties. This estimator has superior performance compared with existing estimators and allows calculation of analytical variances useful for guiding study design. Based on the new estimator we investigate in detail the problem of optimizing the sampling scheme of a biomarker in a vaccine efficacy trial for efficiently estimating its surrogate effect, as characterized by the vaccine efficacy curve (a causal effect predictiveness curve) and by the predicted overall vaccine efficacy using the biomarker.

Keywords

AIDS Vaccines, Clinical Trials as Topic, Vaccines, Biometry, Models, Statistical, immune correlate, two-phase sampling design, principal surrogate, closeout placebo vaccination, estimated likelihood, HIV Infections, Applications of statistics to biology and medical sciences; meta analysis, pseudo-score, Humans, Biomarkers

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
44
Top 10%
Top 10%
Top 10%
bronze
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